Validate NV-based single-molecule conformational sensing in living cells

Validate experimentally, in living cells, the shallow nitrogen-vacancy-center protocol that uses engineered double electron–electron resonance and Bayesian inference to distinguish single-molecule conformations and inter-label distances.

Background

The paper describes a quantum-enhanced protocol using shallow nitrogen-vacancy centers to detect magnetic interactions between two nitroxide electron-spin labels attached to a target molecule. An engineered double electron–electron resonance sequence and Bayesian inference were used to distinguish molecular conformations and inter-label distances under realistic ambient conditions.

The authors explicitly state that the approach has not yet been experimentally validated in living cells. Such validation is necessary to establish whether the simulated and inferred sensing performance transfers to complex intracellular environments, where biological noise, optical backgrounds, and variable molecular conditions may affect the measurement.

References

This approach therefore provides a possible route toward probing single-molecule conformational dynamics, although experimental validation in living cells remains to be demonstrated.

— From Solid-State Spin Defects to Fluorescent Proteins: A Perspective on Quantum Optical Sensing Platforms for Biomedical Applications  (2610.11644 - Parhi et al., 8 Oct 2026) in Section 3, subsection “Probing single molecule dynamics”